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Novel aspects in the pathophysiology and diagnosis of glomerular diseases
  1. Andreas Kronbichler1,2,
  2. Ingeborg Bajema3,
  3. Duvuru Geetha4,
  4. Marcus Säemann5,6
  1. 1Department of Medicine, University of Cambridge, Cambridge, UK
  2. 2Vasculitis and Lupus Service, Addenbrooke’s Hospital, Cambridge, UK
  3. 3Department of Pathology, Leiden University Medical Center, Leiden and Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands
  4. 4Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  5. 56th Medical Department, Nephrology and Dialysis, Clinic Ottakring, Vienna, Austria
  6. 6Medical Faculty, Sigmund Freud University, Vienna, Austria
  1. Correspondence to Dr Andreas Kronbichler, Department of Medicine, University of Cambridge, Cambridge, UK; ak2283{at}cam.ac.uk

Abstract

Immune deposits/complexes are detected in a multitude of tissues in autoimmune disorders, but no organ has attracted as much attention as the kidney. Several kidney diseases are characterised by the presence of specific configurations of such deposits, and many of them are under a ‘shared care’ between rheumatologists and nephrologists. This review focuses on five different diseases commonly encountered in rheumatological and nephrological practice, namely IgA vasculitis, lupus nephritis, cryoglobulinaemia, anti-glomerular basement membrane disease and anti-neutrophil cytoplasm-antibody glomerulonephritis. They differ in disease aetiopathogenesis, but also the potential speed of kidney function decline, the responsiveness to immunosuppression/immunomodulation and the deposition of immune deposits/complexes. To date, it remains unclear if deposits are causing a specific disease or aim to abrogate inflammatory cascades responsible for tissue damage, such as neutrophil extracellular traps or the complement system. In principle, immunosuppressive therapies have not been developed to tackle immune deposits/complexes, and repeated kidney biopsy studies found persistence of deposits despite reduction of active inflammation, again highlighting the uncertainty about their involvement in tissue damage. In these studies, a progression of active lesions to chronic changes such as glomerulosclerosis was frequently reported. Novel therapeutic approaches aim to mitigate these changes more efficiently and rapidly. Several new agents, such as avacopan, an oral C5aR1 inhibitor, or imlifidase, that dissolves IgG within minutes, are more specifically reducing inflammatory cascades in the kidney and repeat tissue sampling might help to understand their impact on immune cell deposition and finally kidney function recovery and potential impact of immune complexes/deposits.

  • immune complex diseases
  • lupus nephritis
  • systemic vasculitis

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Footnotes

  • Handling editor David S Pisetsky

  • AK and IB contributed equally.

  • Correction notice This article has been corrected since it published Online First. The third author affiliation has been updated.

  • Contributors All four authors have contributed to the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests AK received consulting fees from Vifor Pharma, Otsuka, Alexion, UriSalt, Delta4 and Catalyst Biosciences. IB received consulting fees from Boehringer-Ingelheim, Novartis, Catalyst Biosciences and Toleranzia. DG received consulting fees from ChemoCentryx. MS received consulting fees from Astra Zeneca, Boehringer-Ingelheim, Novartis and Otsuka.

  • Provenance and peer review Not commissioned; externally peer reviewed.